Fibrocartilage is important in development and normal functioning of synovial joints. Two major problems involving fibrocartilage are the torn meniscus and the herniated intervertebral disc. The frequency of these lesions and the resultant amount of lost working time make them among the most prominent orthopedic problems in both sports and industrial medicine. Major pathologic changes in marginal fibrocartilage of articular surfaces are observed in osteoarthritis and rheumatoid arthritis, but current concepts of pathogenesis largely ignore its component role. These chronic disesases are the most common disabling and crippling diseases, occur with increasing frequency and severity with aging, and constitute a major component of geriatric medicine. In contrast to the inability of hyaline articular cartilage to undergo effective repair or regeneration, regeneration of meniscal fibrocartilage has been reported though not extensively studied. The limited biochemical information available shown that both of the principal components of fibrocartilage extracellular matrix (collagen and proteoglycan) have distinctly different chemical compositions from those of hyaline cartilage. The overall objectives of the proposed study are to define meniscal and marginal articular fibrocartilage of the normal rabbit knee as a function of development and aging and to define their changes in established rabbit models of traumatic arthritis, degenerative joint disease, and inflammatory joint disease. These studies will assess tissue changes by a combination of histology, cell biology, and extracellular matrix biochemistry. Developmental/aging studies will examine tissue changes during three important stages of musculoskeletal biology: rapid growth, epiphyseal closure, and senescence. Response to trauma will be studied after removal of part of the medial meniscus. Development of osteoarthritis will be studied after immobilization of the knee. An immune synovitis will be used as a model of rheumatoid arthritis. Insights into human disease gained from knowledge of early changes in these animal models may provide a rational basis for the eventual design of new therapeutic methods.